Benzazaborinone derivatives and related compounds



United States Patent 3,293,252 BENZAZABORINONE DERIVATIVES AND RELATED COMPOUNDS Josef Fried, Chicago, Ill., and Frank Herbert Bergeim,

Highland Park, and Harry Louis Yale and Jack Bernstein, New Brunswick, N.J., assignors, by mesne assignments, to E. R. Squibb & Sons Inc., New York,

N.Y., a corporation of Delaware No Drawing. Filed Nov. 12, 1963, Ser. No. 323,058 13 Claims. (Cl. 260--268) This application is a continuation-in-part of application Serial No. 266,484, filed March 20, 1963, which is in turn a continuation-in-part of application Serial No. 140,255, filed September 25, 1961, both now abandoned.

This invention relates to cyclic boron compounds. More particularly, the invention relates to compounds represented by the structural formula.

In the above formula, the symbol R represents hydroxy, alkyl, cycloalkyl, aryl and aralkyl groups. The aryl groups represented by R include the monocyclic phenyl group or bicyelic naphthyl group each of which may in addition hear one or more (preferably up to three) substituents such as lower alkyl, e.g. methyl, ethyl, propyl, isopropyl, butyl and the like, a halogen, e.g. chlorine, bromine, iodine or fluorine, hydroxy, or a lower alkoxy group such as methoxy, ethoxy and the like. In other words the aryl groups represented by R may be expressed as (Y) -phenyl and (Y) naphthy1, Y being hydrogen, halogen, lower alkyl, lower alkoxy or hydroxy and r being an integer from 0 to 3. The aralkyl groups represented by R include the phenyl group, substituted or unsubstituted as described above, attached to a straight or branched chain lower alklene chain. The alkyl groups represented by R are preferably lower alkyl groups such as those illustrated above and the cycloalkyl groups include cycloaliphatic groups, preferably of 3 to 7 carbon atoms, such as cyclopropyl, eyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

R represents aryl and aralkyl as defined above for R. It also represents basic groups such as di-lower alkylamino-lower alkyl groups, e.g., dimethylamin-oethyl, dimethyl aminomethyl, diethylarninoethyl, and the like; the nitrogen of the basic group may also be part of a 5- to 7-membered heterocyclic to form substituents such as N- pyrrolodinomethyl, N-piperidinomethyl, N-piperidinopropyl, N-morpholinomethyl, N -methylpiperazinopropyl,

N hydroxyethylpiperazinoethyl, N methylhomopiperlower alkyl -1ower alkyl-N lower alkyl -lower alkyIene-N (High;

3,293,252 Patented Dec. 20, 1966 -lower alkylene-hl I 0 oHon wherein m is 4 to 6, n is 3 to 5 and R is lower alkyl, hydroxy-lower alkyl or lower alkoxy-lorwer alkyl.

R is representative of hydrogen, halogen, nitro, amino, NH-acyl, N(acyl)R sulfonarnido, lower alkyl, lower alkoxy and haloalkyl. The lower alkyl and lower alkoxy groups are of the character described previously in the discussion of the symbol R. The haloalkyl groups represented by R include monohalogenated groups such as chloromethyl, bromoethyl and the like, as will as polyhalogenated groups such as trifluoromethyl. Any halogen may appear in these substituents.

The acyl groups referred to above are lower alkanoyl groups represented by formyl, aoetyl, propionyl and the like.

X in formula, represents oxygen, sulfur, NH or NR R and R each represents di-lower alkylamino-lower 'alkylene or heterocyclic-lower alkylene groups such as those discussed above with respect to R Preferred in the :class of compounds of Formula I are those in which X represents NH. A second preferred gr-oup constitutes those compounds of Formula I in which the nitrogen adjacent to the keto group bears a 2,6-dialkylphenyl group, especially 2,6-dimethy1phenyl.

The compounds of Formula I are produced by reacting an appropriately substituted 'benzamide, i.e. a compound of the formula wherein R R and X have the meaning already defined, with a b-oronic acid of the formula wherein R has the meaning already defined.

The reaction between the 'benzamide and boronic acid is preferably effected in a non-aqueous medium, e.g. a hydrocarbon solvent such as xylene, toluene, petroleum ether, or the like or another inert solvent such 'as diethyleneglycol dimethyl ether, dioxane, carbon tetrachloride, etc., or mixtures thereof. A mixture of the reactants may be heated and the Water formed in the reaction is removed azeotropically. Anhydrous reactants and solvents contribute to a more effective reaction.

Compounds of this invention include for example,

2,3-dihydro-3 -(2,6-dimethylphenyl) 2-phenyl-1,3,2-

benzodiazaborin-4(1H)-one,

2,3-dihydro-3 (2,6dibromophenyl) -2-phenyl-l ,3,2-

benzodiazabori-n-4( 1H -one,

2,3 -dihydro- 2,6-dimethoxyphenyl) -2- 1 -naphthy1) 1 ,3 ,2-benzodiazaborin-4(1H)-one,

3 -benzyl-2,3-dihydro-2-phenyl-1,3,2-benzodiazabo-rin- 4( 1H -one,

2,3-dihydro-3 (3-dimethylaminopropyl) -2-phenyl-1,3 ,2-

benzodiazaborin-4 1H -one,

3 -(2,6-diethylphenyl)-2,3-dihydro-2-(1-naphthyl)-1,3,2-

benzodiazab orin-4( 1H) -one,

2,3 -dihydro-3-(2,6-dibutylphenyl)-2-(1-naphthyl)-l,3,2-

benzodiazaborin-4(1H)-one,

4 acid in Example 1(c), there obtained the following 2- substituted 2,3 dihydro-3-(2,6-dimethylphenyl)4,3,2- benzodiazaborini- 1H) -ones.

5 Example 2-Substituent in the 2,3-dil1ydr0-3-(2,6- No. Boronio Acid dimethylphenyl) -l,3,2-benzodiazaborin- 4(1H)-one l-naphthyl 2(l-naphthyl). 2-tolyl 2-(2-to1yl).

n-Butyl Z-(mbutyl). Z-phenethyl. 2- (2-phenethyl) Example 12 (a) To g. of isatoci anhydride suspended in 125 In similar fashion, by substituting equivalent amounts of the following boronic acids for the benzene-boronic 23'di .(0'ch1mpheny1)'23'dihydro'l3z'benzothiaza' 15 ml. of 95% ethanol are added d-ropwise 6.4 g. of redis 4 tilled benzylamine. Solution occurs within about 10 2,3-d1hydro-2 mes1tyl-3-naphthyl-l,3,2-benzoth1azabor1nminutes, followed promptly by separation of the product l The mixture is stirred for one hour, cooled and filtered to obtain the product o-arnino-N-benzylbenzamide, which l3.zdbenzodlazab?rm'4(undone is recrystallized from Skellysolve E, M.P. 121-122". -Z- (b) A mixture of 3.14 g. of 2-amino-N benzylbenz- 3 P amide, 1.7 g. of benzeneboronic acid and 100 ml. of 3 d-ry xylene are refluxed for 2.5 hours under a Dean-Stark trap and then cooled. The solid which crystallizes is The compounds of this invention have central depresfiltered p o finlyl 2,3-d1hydro:2phenylsent activity and are useful in psychotherapy. They may l3z'benzodlazabonn'4(u'n'one ,refrystaulzed fmm be administered orally or parenterally in conventional ve- 150 of Skeuysolve 190-192 hicles according to accepted practice.

The following examples are illustrative of the inven- Example 13 h t d l tron All temperatures are stated on t e cen 1gra e sca e To 10 g of isatoic anhydride Suspended in 125 Example 1 m1. of 95% ethanol are added 6.5 g. of redistilled 3- dimethyl-aminopropylamine. The solution is stirred for (a) To of 26'd1methylam1me i of one hour at room temperature and concentrated to dryanhyclmus chlorofonm are adfled 1&6 of ness on a steam bath. The residual oil is distilled, B.P. chloride ,(Prepaled from 0mtmb?nZ01c ac1d and thlonyl 174 (0.05 mm.). The distillate crystallizes spontanechlonde m chloroform) The m 18 refluxed for 1 ously. The product 2-amino-N-(3-dirnethylaminopropyl) hour: the Sohd fi SPSPeHded m f wq benzamide, is recrystallized from Skellysolve E, M.P. momum hydroxide solution and filtered agam to give N- 40 (2,6-dimethy1phenyl)-2-n1trobenzamide, M.P. 210 211. (b) 4.4 of 2 amino N (3dimethylaminopropyl) b) The product from (a) '18 hydrogenated over 5%: beuzamide and 2.44 g. of benzeneboronic acid are re- Palladlum on carbon m absolute Fthanol F about l fiuxed in xylene under a Dean-Stark trap for two hours. and under 50 of Qressure to 'glve i' The hot reaction mixture is filtered and the product al- .methylphenynbenzmde: 130-132 lowed to crystallize in the cooled filtrate. The product, (c) The-product from (b), 2.40 g., 1.22 g. of benzene- 3 (3 dimethylaminopropyn 2,3 dihydm 2 Pheny1 1,3,2 boromc acid and 100 ml. of xylene are refluxed for 4 benzodiazaborimqlH){me is Vacuum dried hours, the water foamed being separated continuously. The cooled reaction mixture deposits 2,3 -dihydro-2-phen- E l 14 yl 3 (2,6 dimethylphenyl)-l,3,2-benzodiazaborin- 4(1H)-one,- M.P. 265-267". (a) 1.0 mole of naphthylmagnesium bromide is pre- In similar fashion, following the procedure of Example pared in dry ether and diluted with an equal volume of 1(a) but substituting an equivalent amount of the followdry toluene to help dissolve the insoluble Grignard reinlg substituted Z-nitrobenzoyl chlorides .for the Z-nitroagent. The incremental addition technique is employed benzoyl chloride in the example, and then utilizing the with tributyl borate at The l-naphthaleneboronic 2-nitrobenzamide derivative thus obtained in the proacid is recrystallized from chlorobenzene, M.P. 203-204". cedure of Example 1(b) to give the Z-aminobenzamide (b) 3.14 g. (0.014 mole) of Z-amino-N-benzylbenzderivative, and the Z-arninobenzamide derivative reacted amide and 2.4 g. (0.014 mole) of l-naphthalene boronic wit-h benzeneboronic acid as in Example 1(c), there are acid and ml. of dry xylene are refluxed under a Deanobtained the following benzenediazaborin-4-(1H)-one 6O Stark trap for 18 hours. The product, 3-benzy1-2,3 d i ti dihydro 2 (l-naphthyl)-1,3,2-benzodiazaborin-4(1H)- Substituent in N-(2,6- Substituent in N-(2,6- Substituent in 2,3-dihydro- Ex. Substituent in 2-nitrodimethylphenyl) Z-nitrodimet-hylphenyl) 2amiuo- 2-phenyl-3-(2,6-dimethyl- No. benzoyl Chloride benzamide beuzauude phenyl)-1,3,2-benzodiazaboriu4-(1H)-oue 4-sulfonamido 4-sulionamido 4-su1ionamid0 7-sulionamido. 4-ehloro.. 4chl0ro 4-cl1loro 7-ehloro. 4-bromo 4-bromo 4br0mo 7-bromo. t methoxyn t-methoxy 4-met-hoxy 7-methoxy. a-sulfonamido 3-snlfnnamidn 3-sulfonamido 8-sull'onamjdo.

3-ehloro 3-ehloro 3-chlom S-ehloro.

one, crystallizes from the cooled reaction mixture and is recrystallized from dry xylene, M.P. 218420.

Example 15 (a) To 21 g. of 6-chloroisatoic anhydride are added 14.3 g. of 3-(N -methylpiperazino)propylamine (prepared from N -methylpiperazinopropyl chloride and phthalimide :followed by hydrolysis. The procedure of Example 13(a) is followed to give 2-amino-N-3-(N"- methylpiperazino -propylb enzamide.

(b) Following the procedure of Example 13(b) but using an equivalent amount of the product from (a) for the 2amino-N-(3-dimethylaminopropyl)benzamide, there is obtained 3-(N -methylpiperazino)propyl-2,3 dihydro-2-phenyl- 1,3,2-benzodiazaborin-4( 1H -one.

Example 16 (a) To 22.4 g. of 6-nitroisatoic anhydride are added 24.2 g. of 2,6-dirnethylaniline and 250 ml. of methanol. The mixture is stirred vigorously and heated under reflux until a clear solution is formed. The methanol is distilled and the residue cooled to give N-(2,6-dimethylphenyl) -2-amino-5-nitrob enz amide.

(b) The procedure of Example 1(c) is followed but an equivalent amount of the product from (a) for the 2-arnino-N-(2,6 dimethylphenyl)benzamide, there is obtained 2,3 dihydro 6 nitro- 2-phenyl-3-(2,6-dimethylphenyl)-1,3,'2-benzodiazaborin-4(1H)-one.

(c) The product from (b), g. and 1 g. 5% palladium on carbon in 200 ml. of absolute ethanol are hydrogenated under 50 lbs. of pressure to give 6-amino-2,3- dihydro 2 phenyl-3-(2,6-dimethylphenyl)-l,3,2-benzodiazaborin-4( 1H -0ne.

(d) The product from (c) 6.8 g. and 3.2 g. of acetyl chloride in 50 ml. of tetrahydrofuran are heated under reflux for 0.5 hr. and concentrated in vacuo to give 6 acetamido 2,3 dihyrdo 2 phenyl 3 (2,6-dimethylphenyl)-1,3 ,2-benzodiazabon'n-4(1H)-one.

(e) The product from (d) 3.83 g., 0.5 g. of sodium hydride and 50 ml. of tetrahydrofuran are stirred and heated under reflux for 1 hour, cooled and 1.4 -g. of 3- dimethylaminopropyl chloride in 10 ml. of tetrahydrofuran added. The mixture is stirred and heated under reflux for 2 hours, filtered and the filtrate concentrated to give 6- (N-acetyl) -N- 3-dimethylaminopropyl) 1amino- 2,3 dihydro 2 phenyl 3 (2,6-dimethylphenyl)-1,3,2- benzodiazaborin-4( 1H -one.

Example 17 By substituting an equivalent amount of 3-(N -methylpiperazino)propyl chloride for the 3-dimethylamino-propyl chloride in Example 16, there is obtained 6-{(N- acetyl) N [3-(N -methylpiperazino)propyl]amino}-2,3- dihydro-2-phenyl-3-(2,6 dirnethylphenyl)-1,3,2-benzodiazaborin-4( 1H) -one.

Example 18 (a) By substituting an equivalent amount of trimethylene chlorobromide for the 3-dimethylaminopropyl chloride in Example 16, there is obtained 6-[(N-acetyl)-N- (3-chloropropyl)] amino-2,3-dihydro-2-phenyl-3-(2,6-dimethylphenyl)-1,3,2-benzodiazaborin-4(1H)-one.

(b) The product from (a) 4.60 g, 2.6 g. of piperazineethanol, 1.5 g. of sodium iodine and 50 ml. of methyl ethyl ketone are stirred and refluxed for 6 hours, filtered, and the filtrate concentrated to dryness to give 6-{(N- acetyl) N [3-(N -methylpiperazino)propyl]amino}2,3- dihydro-2-phenyl-3 (2,6-diimethylphenyl) 1,3,2 benzodiazaborin-4(1H) -one.

Example 19 A mixture of 1.64 g. of N-phenyl-o-aminobenzamide, 1.04 g. of trimethyl borate and 120' ml. of dry xylene is distilled slowly for four hours. During this time the still head temperature rises slowly and reaches a maximum of 120. The clear solution is concentrated to dryness in vacuo. The residual gum is triturated with ether, partial solution occurs and a solid separates. The solid is 6 filtered, air dried, extracted with ml. of Skellysolve E at the boiling point and filtered from the insoluble solid. The filtrate on cooling, deposits a solid, 2,3-dihydro 2 hydroxy-3-phenyl-1,3,2 benzodiaZabo-rin-4(1H)- oue, which is filtered and dried.

Example 20 A solution of 1.85 g. of o-amino-N-benzylbenzamide, 0.85 g. of trimethyl borate and ml. of dry xylene are distilled slowly for two hours. The still head temperature rises slowly from 40 to and a solid separates from the clear solution. The reaction mixture is cooled and the precipitate, a mixture of white and yellow solid, is filtered and dried. The white solid 3-benzyl-2,3-dihydIO-Z-hYdIlOXY-l,3,2-bBDZOdllaZabO1'iI1-4(1H)-011B, is separated mechanically and recrystallized from xylene, M.P. 315.

Example 21 20.6 g. of N-(l-naphthyhsalicylamide and 18.3 g. of benzene-boronic 'acid in 300 ml, of anhydrous toluene are refluxed under a Dean-Stark trap. The toluene solution is filtered while hot and the product crystallizes from solution as the filtrate cools to room tempenature. The white product, 2,3-dihydro-3-'(l-naphthyl)-2-phenyl-l,3,2- benzoxazaborin-4(1H)-one is filtered under suction, washed with toluene, dried in vacuo and recrystallized from acetonitrile, M.P. 201203.

Example 22 (a) To a solution of 19.8 g. of 6-chloro-isatoic anhydride in 200 ml. of 95% ethanol is added 20 ml. of pchloroaniline. The solution which formed is concentrated to give N-(p-chlorophenyl)-5-chloroanthranilamide.

(b) A mixture of 13.1 g. of N-(p-chlorophenyl)-5- chloroanthranilamide, 10.4 g. of trimethyl :borate and 200 ml. of dry Xylene are reacted as in Example 19 to give 6-chloro-3-(p-chlorophenyl)-2,3-dihydro-2-hydroxy 1,3 ,2-benzodiazaborin-4(1H)-0ne.

Example 23 (a) By substituting 17.8 g. of 6-methylisatoic anhyd-ride (prepared from 3-amino-p-toluic acid and phosgene in aqueous potassium carbonate solution) for the 6-chloroisatoic anhydride in Example 2 2 (a) there is obtained N- (p-chlorophenyl) -5-methylanthranilamide.

('b) By substituting 11.6 g. of the product from (a) for the anthran-ilamide compound in Example 221(b) there is obtained 2,3-dihydro-6-methyl-2-hydroxy-3-(pchlonop-henyl)-l,3,2-benzodiazaborin-4(1H)-one.

Example 24 (a) A mixture of 21.5 g. of S-srulfionamido-N-phenylanthranilamide (prepared from 5-sulfoanthranilic acid by treatment first with thionyl chloride in the presence of 1-5% by volume of N,N-dimethylformamide to give the 5-chlorosulfonylanthnaniloyl chloride hydnochloride, followed by treatment first with aniline and then with ammonlia) 15.2 g. Of 4-anisoleboronic acid and 800 ml. of dry xylene are reacted as in Example 22(b) to give 2-(4-anisyl)-2,3-di'hydro-3-phenyl 6 sulfonamido-1,3,2- benzodiazaborin-4-( 1H) -one.

Example 25 (a) By substituting 21.5 g. of 4-sulfionamido-N-phenylranthranilarnide [prepared from 4-sulfonanthranilic acid] for the 5-sulfonamidoanthraniilamide and 17.2 g. of 2- naphthaleneboronic acid for the 4-anis0leboronic 'acid as described in Example 24(a), there is obtained 2,3-dihydro-2-(2 naphthyl)-3-phenyl-7-sulfonamido-1,3,2-benzodiazaborin-4( 1H #one.

Example 26 (a) To a solution of 19.3 g. of anhydrous sodium carbonate in ml. of water is added portionwise 50 g. of anthranilic acid, followed by 50 g.-of 3-dimethylaminopropyl chloride, also added slowly. The mixture is stirred and refluxed for two hours to give 63 g. of N- 3-dimethylaminopropyl) anthranilic acid.

(b) To 15 g. of anhydrous potassium carbonate in 300 ml. of water is added slowly 62.5 g. of the product from (a) above, followed by the slow addition of 37.0 g. of ethyl chloroformate. The precipitated solid is filtered to give 70.3 g. of N-carboxy-N-(3-dimethylaminopropyl) anthranilic acid, N-ethyl ester.

(c) The product from (b) is placed in a preheated oil bath at 220 and heated one-half hour at 220 to give 35.6 g. of 1-(3-dimethylaminopropyl)isatoic anhydride.

(d) The product from (c), 35.0 g., is suspended in 450 m1. of 95% ethanol and ml. o-chloroaniline added. Subsequently, the alcohol solution is concentrated to give 19.8 g. of N-(o-chlorophenyl)-o- (3-dimethylaminopropyl) -aminobenzamide.

(e) The reaction between 2.19 g. of the produce from (d) above and 1.2 g. of benzeneboronic acid is carried out in 100 ml. of dry toluene 'as described in Example 22(b) to give 2.6 g. of 3-(o-chlorophenyl)-2,3-dihydro- 1 (3 dimethylaminopropyl) 2 phenyl 1,3,2 benzodiazaborin-4(1H)-one.

Example 27 A solution of 1.53 g. of N-phenyl thiosali-cylamide, 1.56 g. of o-chlorobenzeneboronic acid and 150 ml. of Skellysolve E (a petroleum ether with a boiling point range of 100-120) is refluxed under a Dean-Stark trap until no more water separates. The hot solution is filtered and the filtrate cooled to give 2.6 g. of 2-(o-chlorophenyl)-2,3-dihydro-3-phenyl 1,3,2 benzothiazaborim 4(lH)-one.

Example 28 By substituting 1.64 g. of mesityleneboronic acid for the benzeneboronic acid in Example 12(b), there is obtained 3 benzyl 2,3 dihydro-Z-mesityl-1,3,2-benzodiazaborin-4( 1H) -one.

Example 29 By substituting 1.76 g. of N-propaneboronic for the benzeneboronic acid in Example 12(b), there is obtained 3 -benzyl-2, 3 -dihydro-2- (n-propyl) -1,3 ,2-benzodiazab orin- 4(1H)-one.

Example 30 Following the procedure of Examples 16(a) and (b), but substituting 7-(trifiuoromethyl)isatoic anhydride as the starting material there is obtained 2,3-dihydro-7-(trifluoromethyl) 2 phenyl-3-(2,6-dimethylphenyl)-1,3,2- benzodiazaborin-4( 1H) -one.

Example 31 By the procedure of Example 21, using the appropriately substituted salicylamide in place of the N-(l-naphthyl) salicylamide and substituted boronic acid (in the manner of Examples 1 to 20) the following compounds are obtained:

8 (trifluoromethyl)-1,3,2-benzoxazaborin-4( 1H) -one; 2,3 -dihydro-2-mesity1-3-benzyl-7-methoxyl ,3 ,2-

benzoxazaborin-4(1H)-one; 2,3-dihydro-2-n-propyl-3-(2,6-dimethylphenyl) -6- methyl-1,3,2-benzoxazaborin-4(1H)-one; 2, 3-dihydro-2-phenyl-3- (2,6-dimethylphenyl) -8- sulfonamido-1,3,2-benzoxazabo1in-4 1H) -one; 2,3-dihydro -2 -phenyl-3 (2,6-dimethylphenyl) -7- methoxy-1,3,2-benzoxazaborin-4( 1H) -one; 2,3-dihydro-2-phenyl-3- (2,6-dimethylphenyl) -8- chloro-1,3,2-benzoxazaborin-4( 1H) -one.

Example 32 By the procedure of Example 27, using the appropriately substituted thiosa-licylamjde in place of the N- phenyl-thiosalicylamide and substituted boronic acid (in the manner of Examples 1 to 20) the following compounds are obtained: 2,3 dihydno-2-phenyl-3-(2,6-dimethylphenyl) 7 (trifiuoromethyl)-1,3,2-benzothiazabo rin-4-(1H)-one; 2,3 dihydro-Q-mesityl-IS-benzyl-l, 3,2-benzothiazaborin 4-(1H)- one; 2,3dihydro-2-'hydroxy 3-(p-ch1orophenyl)-6-methyl 1,3,2-benzothiazaborin-4(1H)-one; 2,3-dihydro-2-phenethyl 3-(2,6 dimethylphenyl)-1,3,2 benzothiazaborin 4(1H)-one; 2, 3-dihydro 2-(n-butyl)-3-(2,6 dimethylphenyl)-1,3,2 benzothiazaborin 4(1H)-one; 2,3-dihydro 2-(2-tolyl)- 3-(2,6-dimethylphenyl) -l,3,2-benzothiazaborin 4(1H)- one; 2,3-dihydro 2-phenyl-3-(2,6 dimethylphenyD-S- chloro-1,3,2-benzothiazaborin-4(1H)-one; 2,3 dihydro- 2 phenyl-3-(2,6-dimethylphenyl)-8 sulfonamido-1,3, 2-benzothiazaborin 4(1H)-one; 2,3-dihydro-2-phenyl-3- 2,6-dimethylphenyl)-7-methoxy 1,3,2 benzothiazaborin- 4 1H) -one; 2,3 -di-hydro-2-phenyl3- (2,6-dimethylphenyl) 7-bromo-1,3,2-benzothiazaborin 4(1H)-one; 2,3-dihydro-Z phenyl-3-(2,6-dimethylphenyl)-7 chlor0-1,3,2- benzothiazaborin 4(1H)-one; 2,3 dihydro-2-phenyl-3- (2,6-dimethylphenyl)-7-sulfonamido 1,3,2 benzothiazaborin-4( 1H)-one.

What is claimed is:

1. A compound of the formula wherein R is a member selected from the group consisting of hydroxy, lower alkyl, cycloalkyl of 3 to 7 carbon atoms, phenyl, naphthyl and phenyl-lowe-r alkyl, R is a member selected from the group consisting of phenyl, naphthyl, phenyl-lower alkyl, di-lower alkylamino-lower alkyl, pyrrolidino-lower alkyl, morpholino-lower alkyl, piperidino-lower alkyl, piperazino-lower alkyl and homopiperazino-lower alkyl; R is a member selected from the group consisting of hydrogen, halogen, nitro, amino, NH- lower alkanoyl, N-(lower aIkanoyD-R, sulfonamido, lower alkyl, lower alkoxy and halo-lower alkyl, R is a member selected from the group consisting of di-lower alkylamino-lower alkyl, pyrrolidino-lower alkyl, morpholino-lower alkyl, piperidino-lower alkyl, piperazinolower alkyl and homopiperazino-lower alkyl; X is a member selected from the group consisting of oxygen, sulfur, NH and N-R R has the same meaning as R each of the foregoing phenyl and naphthyl groups bears 0 to 3 members selected from the group consisting of lower alkyl, halogen, hydroxy and lower alkoxy; and

.each of the foregoing heterocyclic groups bears 0 to 1 member of the group consisting of lower alkyl, hydroxylower alkyl and lower alkoxy-lower alkyl.

2. A compound of the formula ll3-phenyl N lower alkyl-N N-lower alkylene-N C lower [I alkenoyl 3. A compound of the formula ll3-phenyl N ll 0 6. A compound of the formula lower alkyl r:

I -D enyl N 0 ll 0 7. A compound of the formula B-naph thyl N-lower alkylene-phenyl f lower alkyl lower alkyl lower alkanoyl-N H lower alkyl lower alkyl eNO 25 l lower alkyl lower alkyl lower alkyl 8. A compound of the formula 10 B-phenyl N-lower alkylene-N (lower alkyl) 2 9. A compound of the formula 0 2O B-phenyl lower alkyl N lower alkyl 10. A compound of the formula 1I3-pheny1 lower alkyl N (3 lower alkyl 0 11. 2,3 di'hydro 2 phenyl 3 (2,6 dimethylphenyl)-1,3,2-benzodiazaborin-4(1H)-one.

12. 2,3 dihydro 2 naphthyl 3 (2,6 dimethylphenyl)-1,3,2-'benzodiazaborin-4(1H)-one.

13. 3 benzyl 2,3 dihydro 2 phenyl 1,3,2 benzodiazaborin-4(1H)-one. 40

References Cited by the Examiner UNITED STATES PATENTS 3,065,267 11/1962 Lang et al 260551 4 3,135,789 6/1964 Fried et a1. 260-551 OTHER REFERENCES Youngdale et a1.: Jour. Medicinal Chemistry, vol. 7, pages 415 to 427, July 1964.

ALEX MAZEL, Primary Examiner.

H. R. IILES, I. W. ADAMS, Assistant Examiners. 

2. A COMPOUND OF THE FORMULA 